The formation of the myelin sheath by oligodendrocytes in the central nervous system is a complex development process with numerous intermediate steps. Programmed myelin gene expression is regulated both by genetic factors intrinsic to these cells, and by environmental influences encountered as the cells migrate considerable distances from their sites of embryological origin to their final functional target locations. This project aims to increase our understanding of extrinsic factors that are involved in the regulation of oligodendrocyte differentiation and myelin formation and maintenance. The study will use several model systems and assay techniques to address this question at several stages of the overall process of myelinogenesis. One key ingredient in these experiments is our observation that although the culture systems carry out myelinogenesis remarkably normally in many respects, there are differences compared to this process in vivo. Our working hypothesis is that these differences are in many cases due to the absence in the cultures of important growth factor, and that by re-supplying the missing factors, the deficits can be corrected. A second key feature of these systems and the related assays is that they provide quantitative information, often at the level of individual oligodendrocytes. It is expected that these data will contribute to our understanding of oligodendrocyte differentition, thereby providing clues to processes critical to myelin formation, maintenance, and remyelination in both the normal and diseased state.